Synthesis
General procedure for the synthesis of 4-acetamido-piperidine from 4-acetamido-1-benzylpiperidine: preparation of intermediate 40: N-piperidin-4-yl-acetamide (method step 10). Pd-C (350 mg) was added to a solution of N-(1-benzyl-piperidin-4-yl)-acetamide (intermediate 39) (2.3 g, 10.0 mmol) in EtOH (35 mL) and HCl (1 M, 5 mL), and the mixture was stirred for 5 hr under hydrogen atmosphere. Upon completion of the reaction, the catalyst was removed by filtration through diatomaceous earth followed by washing with EtOH and then water. The filtrate was concentrated under vacuum and the product was purified by column chromatography using a methanol solution of dichloromethane/7M NH3 (100:0 to 80:20) as eluent to give the intermediate 40 (0.92 g, 65% yield). Since the compound could not be detected by HPLC-MS, its structure was confirmed by NMR.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 14, p. 2303 - 2306
[2] Organic Process Research and Development, 2012, vol. 16, # 3, p. 470 - 483
[3] Patent: US2012/214798, 2012, A1
[4] Patent: US2005/43298, 2005, A1. Location in patent: Page/Page column 35
[5] Patent: US2005/197333, 2005, A1. Location in patent: Page/Page column 39-40
